title: Damage to the glycoshield activates PMT-directed O-mannosylation via the Msb2-Cek1 pathway in Candida albicans.
abstract: Protein-O-mannosyltransferases (Pmt) transfer mannosyl residues to secretory proteins. Five isoforms of Pmt proteins in the human fungal pathogen Candida albicans have distinct functions in growth, morphogenesis and antifungal resistance. We found that PMT genes encoding the major isoforms Pmt1, Pmt2, Pmt4 are regulated differently in response to impaired glycostructures. While the PMT1 transcript level increased in cell wall mutants and under inhibition of N-glycosylation by tunicamycin, PMT2 and PMT4 transcripts were upregulated only by inhibition of Pmt1 activity. Reporter fusions revealed specific promoter sequences to be required for PMT1 repression in undamaged cells, which was de-repressed by tunicamycin. Constitutive PMT1 de-repression was observed in mutants lacking the Cek1 MAP kinase and its upstream sensor Msb2. In contrast, in msb2 and cek1 mutants, upregulation of PMT2/PMT4 by Pmt1 inhibition did not occur and basal expression of both transcripts were decreased. We identified Ace2 as a novel transcription factor, which upregulates PMT basal expression and induction in response to glycostructure damage. Mutants lacking Msb2, Cek1 and Ace2 were supersensitive to glycosylation and cell wall inhibitors. We propose that a Msb2, Cek1 and Ace2 signalling pathway addresses PMT genes as downstream targets and that different modes of regulation have evolved for PMT1 and PMT2/PMT4 genes.
authors.affiliation: Institut für Mikrobiologie, Molekulare Mykologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1/26.12, 40225 Düsseldorf, Germany.
authors.forename: Pilar D
authors.initials: PD
authors.lastname: Cantero
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Ernst
mesh_terms: D002176:Candida albicans / Q000378:metabolism / Q000502:physiology*; D002473:Cell Wall / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D006801:Humans; D008364:Mannosyltransferases / Q000096:biosynthesis*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; C077339:CEK1 protein, Candida albicans; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; D048052:Mitogen-Activated Protein Kinase 3